Long‐term intrathecal morphine influence on major compounds of the endocrine system in elderly population

Abstract

Background: The influence of long‐term opioid administration on hormonal levels is not well characterized in the literature. We previously showed that intrathecal opioid therapy significantly influences the homeostasis of immune and endocrine systems. Other authors confirmed that exogenous and endogenous opioids induce this effect. They have a cytokine‐like behavior and may function as neurotransmitters, neuromodulators or hormones, as concerning their synthesis, storage and release. Aims: To assess the effects of morphine long‐term intrathecal administration on serum levels of Gonadal, Thyroidal and Adrenal axis hormones in an elderly population affected by chronic pain; to assess the correlation between hormone levels and morphine dosage. Methods: Patients suffering from chronic non‐cancer pain with or without intrathecal drug delivery system were studied and hormonal levels were monitored, using an immunoradiometric assay kit. Results: The long‐term administration of intrathecal morphine influenced part of the endocrine system, in particular, there was a reduction of FSH and LH and an increment of GH serum levels; this effect was morphine dose dependent. Conclusion: Long‐term intrathecal opioid administration influenced FSH, LH and GH serum levels. Data on this issue are inadequately described in the literature. The finding of endocrine effects of opioid therapy, nonetheless, cannot be ignored, as it may have clinical relevance in both elderly and young population. We believe that during long intrathecal pain treatments with morphine, clinicians should be aware of both immediate and later opioids side effects, and in particular, they should monitor immune and endocrine changes.

Long‐term opioid treatment and endocrine measures in chronic non‐cancer pain patients: A systematic review and meta‐analysis

“…The overall risk of bias of the RCT (Mueller et al, 2018) was high due to a combination of insufficient information regarding randomization and blinding procedures (Table S2). The overall risk of bias of the three before-andafter studies (Aurilio et al, 2011;Ozyuvaci et al, 2004;Roberts et al, 2002) and the nine cross-sectional studies (Aloisi et al, 2005;Daniell, 2008;Duarte et al, 2013;Gibb et al, 2016;Lamprecht et al, 2018;Nenke et al, 2015;Raffaeli et al, 2009;Valverde-Filho et al, 2015;Wong et al, 2011) was fairly high, especially due to sample size and comparability (Table S2).…”

Intrathecal Drug Administration for the Treatment of Cancer and Non-Cancer Chronic Pain

“…In the last years data have been accumulated on the biological effects of systemic administration of morphine (50)(51)(52). Less is known about the effects of spinaly administered opioids on various body systems which are not purely nociceptive.…”

“…Animals and humans studies have explored both the acute and the chronic neuroendocrine effects of opiates and different opioid peptides. Acute administration of opioids in humans increases the secretion of PRL, growth hormone (GH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) while it inhibits the release of luteinizing hormone (LH) (64,52). It has been argued that the inhibition of LH release is mediated through central inhibition of hypothalamic GnRH secretion (65).…”

Long-term intrathecal morphine and bupivacaine upregulate MOR gene expression in lymphocytes

“…These effects on the immune system were dependent on the administration route, with IT administration being a stronger inhibitor of LAK cytotoxicity [10]. [11][12][13][14].…”